General Anesthesia With Xenon in Inspiratory Concentrations of 50% and 70% and Total I.V. Anaesthesia.

An International Phase III Randomised Trial Comparing the Propofol Consumption During General Anaesthesia With Xenon in Inspiratory Concentrations of 50% and 70% and Total I.V. Anaesthesia Alone in ASA III Patients With Increased Risk of Perioperative Cardiac Complications.

The purpose of this study is to evaluate the quantity of propofol administered with Xenon in two inspiratory concentrations, to maintain comparable depth of anaesthesia during the maintenance period of general anaesthesia.

Study Overview

• Status: Terminated
• Conditions: Anaesthesia
• Intervention / Treatment: Drug: Xenon; Drug: Xenon; Drug: Medical Air in Oxygen

Detailed Description

The inert or "noble" gas Xenon has anaesthetic properties that have been recognized 50 years ago. Several preclinical studies and investigations using xenon as an inhalational anaesthetic in humans were performed and reported that this gas has many properties of the ideal anaesthetic agent. Moreover, it is known that when xenon is combined with volatile anaesthetics or opioids, the required doses of those substances are reduced, resulting in a lower incidence of side effects. Patients could benefit from the administration of xenon if this inspired concentration would result in reduced doses of co-administered drugs.

This trial should allow evaluating the propofol consumption required in combination with xenon administered in inspiratory concentrations of 50% and 70% to maintain comparable depth of general anaesthesia as total i.v. anaesthesia, in ASA III patients presenting increased risk of perioperative cardiac complications and undergoing laparotomy or orthopaedic surgery.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63058
    • Centre Hospitalier Universitaire de Clermont-Ferrand
  • Nîmes, France, 30029
    • Groupe Hospitalier Universitaire Caremeau
• Germany
  • Berlin, Germany, D-14129
    • Evangelisches Waldkrankenhaus Berlin-Spandau
  • Halle, Germany, D-06112
    • BG Kliniken-Bergmannstrost
  • Kiel, Germany, D-24105
    • University Hospital Schleswig-Holstein
• United Kingdom
  • Manchester, United Kingdom, M139WL
    • Manchester Royal Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient ≥ 50 years old
• ASA (American Society of Anaesthesiologists) Physical Status III
• Patient with increased risk of perioperative cardiac complications (Revised Cardiac Risk Index>=2)
• Surgical operation: laparotomy or orthopaedic surgery or laparoscopy
• Planned duration of general anaesthesia in the range of 2-6 hours
• Patient willing and able to complete the requirements of this study including the signature of the written informed consent

Exclusion Criteria:

• Patient with severe impairment of cardiac function (Left Ventricular Ejection Fraction < 35%)
• Patient with drug-eluting stent placed within 12 months prior to selection
• Woman of child-bearing potential not implementing adequate contraceptive methods
• Pregnant or lactating woman
• Surgical procedure in emergency
• Chronic opioids pain therapy

• Serious illness or medical conditions which are possible contra indication for elective general anaesthesia or administration of intra operative treatments, or which are interfering with the monitoring devices, such as:

  • Myocardial infarction within 6 months prior to selection
  • Any significant history of allergy/hypersensitivity to any drugs used during the study, to silicone or to latex
  • Severely impaired hearing
  • Known severe neurological disorders
  • Any medical condition which does not justify the trial participation in the investigator's judgement
  • General anaesthesia within 7 days prior to selection
  • Laparotomy within 3 months prior to selection, only for patients undergoing laparotomy
• History of drug abuse or psychiatric disorders which would impair the understanding of the necessary information or render medically or legally not able to give written informed consent
• Concurrent treatment with any other experimental drugs
• Participation in any other clinical trial within 4 weeks prior to selection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Xenon 50% (45%-55%) in Oxygen (45%-55%),	Drug: Xenon; Maintenance of anaesthesia obtained with Xenon 50% and propofol infusion adjusted to depth of anaesthesia.; Drug: Xenon; Maintenance of anaesthesia obtained with Xenon 70% and propofol infusion adjusted to depth of anaesthesia.
Experimental: Group B; Xenon 70% (65%-75%) in Oxygen (25%-35%)	Drug: Xenon; Maintenance of anaesthesia obtained with Xenon 50% and propofol infusion adjusted to depth of anaesthesia.; Drug: Xenon; Maintenance of anaesthesia obtained with Xenon 70% and propofol infusion adjusted to depth of anaesthesia.
Active Comparator: Group C; Medical Air in Oxygen (45%-55%)	Drug: Medical Air in Oxygen; Maintenance of anaesthesia obtained with propofol infusion adjusted to depth of anaesthesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose of Propofol (mg) Administered During Maintenance Adjusted to Patient Body Surface Area (BSA in m²) and Maintenance Duration (Min)	Dose of propofol administered with a Target Controlled Infusion (TCI) device, cerebral concentration equal to 5 µg/mL at the end of induction, and then concentration adjusted to the level of depth of anaesthesia during maintenance. Depth of anaesthesia continuously assessed by signals derived from electroencephalographic recording. Analgesia during induction and maintenance obtained with remifentanil administered with a second TCI device at the stable cerebral concentration of 7 ng/mL.	Maintenance period (1 Day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anaesthesia Recovery Time	Time interval between the end of maintenance period and time of tracheal tube removal.	1 Postoperative Day
Awakening Time	Time interval between the end of maintenance period and time of Aldrete score ≥ 9.	1 Postoperative Day
Stay in the Operating Room	Time interval between admission in the operating room and discharge from the operating room.	1 Postoperative Day
Stay in the Recovery Room	Time interval between admission in the recovery room and discharge from the recovery room.	1 Postoperative Day
Haematology - Leucocytes (Giga/L)	Leucocytes (Giga/L) obtained from blood samples collected at baseline and in the morning following surgery.	1 Postoperative Day
Haematology - Erythrocytes (Tera/L)	Erythrocytes (Tera/L) obtained from blood samples collected at baseline and in the morning following surgery.	1 Postoperative Day.
Haematology - Platelets (Giga/L)	Platelets (Giga/L) obtained from blood samples collected at baseline and in the morning following surgery	1 Postoperative Day
Serum Chemistry - AST (GOT) (IU/L)	AST (GOT) (IU/L) obtained from blood samples collected at baseline and in Morning following surgery.	1 Postoperative Day
Serum Chemistry - ALT (GPT) (IU/L)	ALT (GPT) (IU/L) obtained from blood samples collected at baseline and in Morning following surgery	1 Postoperative Day
Serum Chemistry - Gamma GT (IU/L)	Gamma GT (IU/L) obtained from blood samples collected at baseline and in Morning following surgery	1 Postoperative Day
Serum Chemistry - Creatinine (Mcmol/L)	Creatinine (mcmol/L) obtained from blood samples collected at baseline and in Morning following surgery	1 Postoperative Day
Serum Chemistry - Urea (mmol/L)	Urea (mmol/L) obtained from blood samples collected at baseline and in Morning following surgery	1 Postoperative Day

Collaborators and Investigators

• Sponsor: Air Liquide SA
• Investigators: Principal Investigator: Berthold BEIN, Prof Dr Med, University Hospital Schleswig-Holstein; Study Chair: Jens SCHOLZ, Prof. Dr Med, University Hospital Schleswig-Holstein

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: June 11, 2009
• First Submitted That Met QC Criteria: June 11, 2009
• First Posted (Estimate): June 12, 2009

Study Record Updates

• Last Update Posted (Estimate): September 25, 2014
• Last Update Submitted That Met QC Criteria: September 15, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Xenon in Anaesthesia
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Xenon
• Other Study ID Numbers: ALMED-07-C3-007; 2007-001979-10